Table 1.

Adipokines and the regulatory effect on intestinal homeostasis.

Adipokine	Effect on mucosal homeostasis	References
Adiponectin	Function Adiponectin plays a key role in regulating insulin sensitivity. In addition, an anti-inflammatory effect has been demonstrated for atherosclerosis.	(4)
	in vitro Globular adiponectin has been shown to enhance intestinal epithelial cell proliferation and prevented these cells from apoptosis. In line, adiponectin−/− mice developed more severe DSS-induced colitis accompanied by a decreased epithelial proliferation, increased apoptosis and cellular stress. This could be reversed in vitro in the presence of adiponectin.	(5, 6)
	in vivo models The data on the in vivo role are controversial. Fayad et al. provided evidence suggesting a pro-inflammatory role for adiponectin in DSS- as well as TNBS-induced colitis. Conversely, Nishihara et al. found the opposite. In addition, work by Sideri et al. demonstrated that silencing of AdipoR1 was followed by deterioration of TNBS-induced colitis. These obvious discrepancies might be explained by differences in knockout mice.	(7–10)
	Human data Adiponectin has been shown to be upregulated in the creeping fat of Crohn's disease as compared to non-creeping fat of Crohn's disease, ulcerative colitis and healthy controls.	(11)
Apelin	Function Apelin induces proliferation of intestinal epithelial cells. Apelin plays a role in the development and stabilization of lymphatic vessels.	(12)
	in vivo models Apelin is upregulated in the intestinal epithelial cells of colitic mice. Apelin administration ameliorated colitis in Il10−/− mice by enhancing intestinal lymphatic function.	(13, 14)
	Human data Apelin is upregulated in the intestinal epithelial cells of IBD patients. Apelin is highly expressed in the mesenteric adipose tissue of Crohn's disease patients.	(12, 15)
Chemerin	Function Chemerin has been shown to serve as chemoattractant for cells of the innate immune system.	(16)
	in vivo models Administration of chemerin aggravated DSS-induced colitis and was associated with a decrease in anti-inflammatory macrophages. Accordingly, mice deficient in the chemerin receptor, chemokine-like receptor 1 (CMKLR1), develop colitis in a delayed course, ultimately resulting in similar disease severity.	(17, 18)
	Human data Chemerin was elevated in the serum of IBD patients.	(19)
Leptin	Function Leptin was initially identified as a hormone and satiety factor. Early work revealed an enhancing effect on T cell proliferation and polarization.	(2, 20)
	in vitro Leptin has been shown to induce an increased intestinal epithelial cell proliferation. In addition, intestinal epithelial cells produce leptin and luminal leptin vice versa activates the NF- κB pathway in intestinal epithelial cells. In line, rectal application in vivo results in intestinal inflammation. Leptin signaling is required for in vitro polarization of Th17 cells as leptin receptor (Lepr) deficient T cells display decreased STAT3 signaling and consecutively less RORγt expression and impaired IL-17 and IFNγ production.	(21–23)
	in vivo models Leptin-deficient ob/ob mice are protected from experimental colitis. Colitis induction depends on the activation of T cells by leptin as proven in the T cell transfer model of colitis. Leptin produced by T cells does not contribute to colitis development.	(24–27)
	Human data Leptin is upregulated in the mesenteric fat of Crohn's disease patients. The presence of leptin in the mesenteric fat favors the polarization of tissue macrophages toward an anti-inflammatory phenotype.	(28, 29)

AdipoR1, adiponectin receptor type 1; DSS, dextran sodium sulfate; IBD, inflammatory bowel diseases; NF- κB, nuclear factor “kappa-light-chain-enhancer” of activated B-cells; TNBS, trinitrobenzene sulphonic acid.